Ournal of KJMS Established in 1985
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Kaohsiung Journal of Medical Sciences
Letter To the Editor
The coexistence of Cushing syndrome and gynecomastia as the manifestations of adrenocortical carcinoma
Dear editor,
A 43-year-old man presented with gynecomastia for 4 months. He also complained about loss of libido and 3-kg weight gain. Bilateral gynecomastia with testicular atro- phy was noted as well as his Cushingoid appearance on the physical exam. Computed tomography scan showed a huge heterogeneous hypoechoic left suprarenal mass (Fig. 1A) corresponding to the palpable abdominal mass. Multiple metastatic lung nodules were also detected (Fig. 1B). The diagnosis of feminizing adrenocortical carcinoma (ACC) with Cushing syndrome was proposed by elevated UFC (606.02 µg/24 h, 21-143) with low ACTH level, and hyperestrogenemia (1221 pmol/L, 0-130). Left adrenalectomy, nephrectomy with splenectomy and IVC thrombectomy were performed. The pathological study showed a tumor size of 12 x 13 x 15 cm with extensive necrosis and capsular invasion, Ki-67 was 10% positive. Postoperatively, mitotane was commenced to control his advanced tumor. His gynecomastia subsequently regressed as well as his estradiol levels decreased. Un- fortunately, he died six months later due to the uncon- trolled infection.
Gynecomastia, an enlargement of male breast, is a common disorder in clinical practice. It represents a femi- nizing condition due to either absolute or relative estrogen excess. Causes of hyperestrogenemia include exogenous administration and endogenous overproduction from secreting tumors or increased peripheral aromatization; whereas relative estrogen excess refers to a decrease in androgen levels or its actions. An initial step in making the diagnosis is to differentiate from lipomastia and breast cancer. True gynecomastia is characterized by a rubbery mass concentric within the nipple-areolar complex [1].
Most cases have a benign etiology from physiologic changes or medications; however, few cases can be a result of un- derlying endocrine disorders or tumors. Feminizing tumors can be categorized into estrogen-producing testicular or adrenal tumors and hCG-producing testicular or non- testicular tumors. Several possible causes can be uncov- ered with an extensive history and physical examination: onset/duration, tenderness, medications, family history of gynecomastia or neurological diseases, systemic diseases (liver or renal failure), and endocrine disorders (hyper- estrogenemia, hypogonadism, thyrotoxicosis). Initial in- vestigations should include a liver/renal function, hormonal profiles (testosterone, estradiol, LH, TSH, prolactin) and tumor markers (hCG, a-fetoprotein); nonetheless, about one-fourth would be classified as idiopathic.
ACC is a rare tumor with dismal prognosis. Adjacent organ invasion or metastasis is crucial to distinguish from the benign lesions. Larger size (>4 cm), sex hormone excess (virilization/feminization), high mitotic figures or capsular/vascular invasion are also characteristics of ACC [2]. Nearly 60% of ACC is functional, predominantly with a cortisol excess, a whereas feminizing tumor is found in only 2-6% [2,3]. Hyperestrogenemia in ACC has been attributed to an increased tumoral aromatase ac- tivity. Another possible mechanism is the peripheral conversion of weaker androgens from the tumor [4]. Feminizing tumor is manifested mainly by symptoms of hyperestrogenism (e.g. gynecomastia, testicular atro- phy, and erectile dysfunction), mass symptoms or dete- rioration of the general conditions (fatigue, weight loss). As described in our patient, multiple hormonal secretions represent its de-differentiated tumorigenesis and ste- roidogenic dysregulations. Therefore, complete hor- monal evaluation is requisite in ACC patients even if clinical symptoms are absent to prevent adrenal insuffi- ciency postoperatively and provide as a marker of tumor
Conflicts of interest: All authors declare no conflicts of interests.
A
Arterial\Phase
P
cm
B
P
Venous\Phase\Cor V-5/3.19
cm
recurrence [5]. Complete surgical removal is the only curative treatment. Mitotane and chemotherapy are adjunctive modalities to control an advanced disease.
In conclusion, gynecomastia is common and self-limited but few cases can be from a malignant cause. Further investigation is required when it occurs in an unusual age group or is progressive.
Appendix A. Supplementary data
Supplementary data related to this article can be found at https://doi.org/10.1016/j.kjms.2018.06.004.
References
[1] Narula H, Carlson HE. Gynaecomastia-pathophysiology, diag- nosis and treatment. Nat Rev Endocrinol 2014;10:684-98.
[2] Kidd MT, Karlin NJ, Cook CB. Feminizing adrenal neoplasms: case presentations and review of the literature. J Clin Oncol 2011;29:e127-30.
[3] Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, et al. Adrenocortical carcinoma. Endocr Rev 2014;35:282-326.
[4] Hatano M, Takenaka Y, Inoue I, Homma K, Hasegawa T, Sasano H, et al. Feminizing adrenocortical carcinoma with distinct histopathological findings. Intern Med 2016;55: 3301-7.
[5] Fassnacht M, Kroiss M, Allolio B. Update in adrenocortical carcinoma 2013;98:4551-64.
Mongkontida Umphonsathien Endocrinology Unit, Department of Medicine, Police General Hospital, Bangkok, Thailand
Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Panudda Srichomkwun Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Excellence Center in Diabetes, Hormones and Metabolism, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Patinut Buranasupkajorn Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Excellence Center in Diabetes, Hormones and Metabolism, King Chulalongkorn Memorial Hospital, Bangkok, Thailand Division of Hospital and Ambulatory Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Thiti Snabboon* Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Excellence Center in Diabetes, Hormones and Metabolism, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
*Corresponding author. Excellence Center in Diabetes and Metabolism, BhumiSirimangalanusorn Bldg, 4C fl., King Chulalongkorn Memorial Hospital, Rama IV Road, Patum- wan, Bangkok, 10330, Thailand.
E-mail address: Thiti.S@chula.ac.th